Proc Natl Acad Sci U S A. 2005 Feb 8;102(6):1911-4. Epub 2005 Jan 21.

Inositol pyrophosphates regulate cell death and telomere length through phosphoinositide 3-kinase-related protein kinases.

Saiardi A, Resnick AC, Snowman AM, Wendland B, Snyder SH.

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Department of Neuroscience, Pharmacology and Molecular Sciences, and Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.

Abstract

Inositol pyrophosphates physiologically regulate vesicular endocytosis, ribosomal disposition, and directly phosphorylate proteins. Here we demonstrate roles in cell death and regulation of telomere length. Lethal actions of wortmannin and caffeine are selectively abolished in yeast mutants that cannot synthesize inositol pyrophosphates. Wortmannin and caffeine appear to act through the phosphoinositide 3-kinase-related protein kinases Tel1 and Mec1, known regulators of telomere length. Inositol pyrophosphates physiologically antagonize the actions of these kinases, which is demonstrated by the fact that yeast mutants with reduced or elevated levels of inositol pyrophosphates, respectively, display longer and shorter telomeres.

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Proc Natl Acad Sci U S A. 2005 Feb 8;102(6):1811-2.

PMID:: 15665079; [PubMed - indexed for MEDLINE]
PMCID:: PMC548528

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